Biosensor

ABSTRACT

A biosensor is provided in accordance with the present invention. The biosensor includes an electrode support substrate, electrodes positioned on the electrode support substrate, a sensor support substrate coupled to the electrode support substrate, and electrically conductive tracks positioned on the sensor support substrate. Each track is in electrical communication with one of the electrodes.

FIELD OF THE INVENTION

The present invention relates to a biosensor, more particularly to anelectrochemical biosensor with a hybrid electrode.

BACKGROUND AND SUMMARY OF THE INVENTION

Electrochemical biosensors are known. They have been used to determinethe concentration of various analytes from biological samples,particularly from blood. Electrochemical biosensors are described inU.S. Pat. Nos. 5,413,690; 5,762,770; 5,798,031; and 5,997,817 thedisclosure of each of which is expressly incorporated herein byreference.

According to one aspect of the present invention an electrochemicalbiosensor is provided. The biosensor comprises an electrode supportsubstrate, electrodes positioned on the electrode support substrate, asensor support substrate coupled to the electrode support substrate, andelectrically conductive tracks positioned on the sensor supportsubstrate, each track being in electrical communication with one of theelectrodes.

According to another aspect of the present invention an electrochemicalbiosensor is provided. The biosensor comprises a metallized electrodesupport substrate defining an electrode array and leads extending fromthe array, a sensor support substrate coupled to the electrode supportsubstrate, the sensor support substrate being formed to include notchesand an opening, at least a portion of each notch being aligned with onelead and the opening being spaced-apart from the leads, andelectrically-conductive tracks positioned on the sensor supportsubstrate. Each track extends across one of the notches and intoengagement with one lead.

According to still another aspect of the present invention a method offorming a biosensor is provided. The method comprises the steps ofproviding a metallized electrode support substrate and a sensor supportsubstrate, ablating the electrode support substrate to form electrodes,coupling the sensor support substrate to the electrode supportsubstrate, and positioning spaced-apart electrically conductive tracksacross the sensor support substrate so that each track is in electricalcommunication with one electrode.

Additional features of the invention will become apparent to thoseskilled in the art upon consideration of the following detaileddescription of the preferred embodiment exemplifying the best mode ofcarrying out the invention as presently perceived.

BRIEF DESCRIPTION OF THE DRAWINGS

The detailed description particularly refers to the accompanying figuresin which:

FIG. 1 is an exploded assembly view of a biosensor in accordance withthe present invention, showing the biosensor including an electrodesupport substrate, laser-ablated electrodes on the electrode supportsubstrate, a sensor support substrate, electrically-conductive tracksformed to be positioned on the sensor support substrate and inengagement with the laser-ablated electrodes, and a cover substrate.

FIG. 2 is a cross-sectional view taken through lines 2—2 of FIG. 1showing a liquid blood sample entering the biosensor.

FIG. 3 is an exploded assembly view of a biosensor in accordance withanother aspect of the present invention.

FIG. 4 is a plan view of the biosensor of FIG. 3.

FIG. 5 is an exploded assembly view of a biosensor in accordance withanother aspect of the present invention.

FIG. 6 is a cross-sectional view taken through lines 6—6 of FIG. 5.

FIG. 7 is a cross-sectional view taken through lines 7—7 of FIG. 5.

FIG. 8 is an exploded assembly view of a biosensor in accordance withanother aspect of the present invention.

FIG. 9 is a cross-sectional view of FIG. 8.

DETAILED DESCRIPTION OF THE DRAWINGS

The present invention relates to a biosensor and a method formanufacturing a biosensor that provides a manufacturer with flexibilityin electrode design variation. The biosensor uses a high-end processsuch as laser ablation to produce sensitive parts of the biosensor anduses a screen-printing process to make meter contacts. Thus, by simplychanging a sensor support substrate and/or a cover substrate as well asthe electrode ablation pattern multiple products can be produced fromthe same manufacturing system to meet market needs. Various aspects ofthe invention are presented in FIGS. 1-9, which are not drawn to scaleand wherein like components in the several views are numbered alike.

FIGS. 1-2 illustrate an aspect of the invention in the form of abiosensor 10 having a sensor support substrate 12, an electrode supportsubstrate 14, a first electrical conductor 16 positioned on theelectrode support substrate 14, an electrochemical reagent 20 positionedon first conductor 16, a first electrically-conductive track 60 and asecond electrically-conductive track 62 each extending across the sensorsupport substrate 12, and a cover substrate 21. Biosensor 10 ispreferably rectangular in shape. It is appreciated, however, thatbiosensor 10 can assume any number of shapes in accordance with thisdisclosure. Biosensor 10 is preferably produced from rolls of material,however, it is understood that biosensor 10 can be constructed fromindividual sheets in accordance with this disclosure. Thus, theselection of materials for the construction of biosensor 10 necessitatesthe use of materials that are sufficiently flexible for roll processing,but which are still rigid enough to give a useful stiffness to finishedbiosensor 10.

The electrode support substrate 14 is shown in FIGS. 1 and 2, andincludes a top surface 40 facing sensor support substrate 12 and abottom surface 42. In addition, electrode support substrate 14 hasopposite ends 44, 46 and opposite edges 48, 50 extending between ends44, 46. Edge 48 includes a notch 49 formed therein. Notch 49 is definedby boundaries 51, 53, 55. In addition, a vent opening 57 extends betweentop and bottom surfaces 40, 42. Vent opening 57 may have a wide varietyof shapes and sizes in accordance with this invention. Electrode supportsubstrate 14 is generally rectangular in shape, it is appreciated,however, that support may be formed in a variety of shapes and sizes andnotch 49 can be positioned in a variety of locations in accordance withthis disclosure. Electrode support substrate 14 is formed from aflexible polymer and preferably from a polymer such as a polyester orpolyimide, polyethylene naphthalate (PEN). A non-limiting example of asuitable PEN is 5 mil thick KALADEX®, a PEN film commercially availablefrom E.I. DuPont de Nemours, Wilmington, Del., which is coated with goldby ROWO Coating, Henbolzhelm, Germany.

Electrical conductor 16 is created or isolated on top surface 40 ofelectrode support substrate 14. Non-limiting examples of a suitableelectrical conductor 16 include aluminum, carbon (such as graphite),cobalt, copper, gallium, gold, indium, iridium, iron, lead, magnesium,mercury (as an amalgam), nickel, niobium, osmium, palladium, platinum,rhenium, rhodium, selenium, silicon (such as highly dopedpolycrystalline silicon), silver, tantalum, tin, titanium, tungsten,uranium, vanadium, zinc, zirconium, mixtures thereof, and alloys,oxides, or metallic compounds of these elements. Preferably, electricalconductor 16 is selected from the following materials: gold, platinum,palladium, iridium, or alloys of these metals, since such noble metalsand their alloys are unreactive in biological systems. Most preferably,electrical conductor 16 is gold.

Conductor 16 is disrupted to create electrodes 52, 54 on electrodesupport substrate 14 that are isolated from the rest of the electricallyconductive surface by laser ablation. Techniques for forming electrodeson a surface using laser ablation are known. See, for example, U.S.patent application Ser. No. 09/411,940, filed Oct. 4, 1999, and entitled“LASER DEFINED FEATURES FOR PATTERNED LAMINATES AND ELECTRODE”, thedisclosure of which is expressly incorporated herein by reference.Preferably, electrodes 52, 54 are created by removing the electricalconductor 16 from an area extending around the electrodes.

Therefore, electrodes 52, 54 are isolated from the rest of theelectrically-conductive material on electrode support substrate 14 by agap having a width of about 25 μm to about 500 μm, preferably the gaphas a width of about 100 μm to a about 200 μm. Alternatively, it isappreciated that electrodes 52, 54 may be created by laser ablationalone on electrode support substrate 14. It is appreciated that whilelaser ablation is the preferred method for forming electrodes 52, 54given its precision and sensitivity, other techniques such aslamination, screen-printing, or photolithography may be used inaccordance with this disclosure.

Electrodes 52, 54 cooperate with one another to define an electrodearray 56 and leads 58, 59 that extend away from array 56. As shown inFIG. 1, leads 58, 59 extend from array 56 to contact pads 61, 63respectively. Contact pads 61, 63 are located at respective edges 48,50. It is appreciated that array 56 and contact pads 61, 63 can have avariety of shapes and sizes and leads 58, 59 can be formed to have manylengths and extend to a variety of locations so that contact pads 61, 63can be located on electrode support substrate 14.

Multi-electrode set arrangements are also possible in accordance withthis disclosure. It is appreciated that the number of electrodes, aswell as the spacing between the electrodes may vary in accordance withthis disclosure and that a number of arrays may be formed (FIGS. 8-9) aswill be appreciated by one of skill in the art.

Sensor support substrate 12 of biosensor 10 includes a first surface 22and an opposite second surface 24 facing electrode support substrate 14.See FIGS. 1 and 2. In addition, sensor support substrate 12 has oppositeends 26, 28 and edges 30, 32 extending between ends 26, 28. An opening34 extends between first and second surfaces 22, 24 as shown in FIG. 1.In addition, notches 36, 38 are formed in edges 30, 32 respectively,which are spaced-apart from opening 34. As shown in FIG. 1, opening 34is defined by boundaries 78, 80, 82 and tapers 843 that extend betweenedge 30 and boundaries 78, 82. In addition, notches 36, 38 are eachdefined by boundaries 84, 86, 88.

When sensor support substrate 12 is coupled to electrode supportsubstrate 14, tapers 83 are in general alignment with boundaries 51, 55of electrode support substrate 14 such that opening 34 exposes electrodearray 56 and reagent 20. In addition, notches 36, 38 are in generalalignment with contact pads 61, 63 of electrodes 52, 54. It isappreciated that notches 36, 38 can be located in a number of locationsand formed in a variety of shapes and sizes in sensor support substrate12 in accordance with this disclosure. It is also appreciated thatsensor support substrate 12 may be formed without notches in accordancewith this disclosure, so long as tracks 60, 62 are in electricalcommunication with electrodes 52, 54. Sensor support substrate 12 isformed of a flexible polymer and preferably from a polymer such aspolyester. A non-limiting example of a suitable polymer is 7 mil thickST505 MELENEX® polyester film commercially available from E.I. DuPont deNemours, Wilmington, Del.

Additionally, while not illustrated, surface 24 of sensor supportsubstrate 12 is coated with an adhesive. Preferably, sensor supportsubstrate 12 is coupled to electrode support substrate 14 with athermoset adhesive. A non-limiting example of such an adhesive is ablend of item #38-8569 (5% wt./wt. isocyanate) and item #38-8668 (95%wt./wt. polyurethane), both commercially available from National Starch&Chemical, a Member of ICI Group, Bridgewater, N.J. It is appreciatedthat substrate may be coupled to electrode support substrate 14 using awide variety of commercially available adhesives or with welding (heator ultrasonic) in accordance with this disclosure. It is alsoappreciated that first surface 22 of sensor support substrate 12 may beprinted with, for example, product labeling or instructions for use inaccordance with this disclosure.

Referring again to FIG. 1, first and second tracks 60, 62 formed to bepositioned on first surface 22 of sensor support substrate 12. Tracks60, 62 each extend from end 28 and across one of the notches 36, 38.While track 60, notch 38, and electrode 54 will be discussed hereafter,it is appreciated that unless indicated otherwise, the descriptionapplies to track 62, notch 36, and electrode 52 as well. Track 60includes a first layer 64 and a second layer 66. Preferably first layer64 includes opposite ends 90, 92 and edges 94, 96 extending between ends90, 92. As shown in FIGS. 1 and 2, upon assembly of biosensor, a portion98 of first layer 64 extends downwardly from first surface 22 of sensorsupport substrate 12 into notch 38 and engages electrode 54. In thismanner, first layer 64 is in electrical communication with electrodes52, 54 of electrode support substrate 14. Second layer 66 of tracks 60includes opposite ends 100, 102 and edges 104, 106 extending betweenends 100, 102. In addition, a portion 108 of second layer 66 is alignedwith portion 98 of first layer 64. Thus, second layer 66 is inelectrical communication with electrodes 52, 54 via the first layer 64upon assembly of biosensor 10.

Tracks 60, 62 are preferably screen-printed onto sensor supportsubstrate 12. The method of forming tracks 60, 62, however, is notlimited. While direct contact between track 60 and electrode 54 isillustrated and described, it is appreciated track 60 and electrode 54may not be in direct contact with one another so long as there is anelectrical connection between the two, i.e. vias or other methodsappreciated by those skilled in the art.

Non-limiting examples of suitable electrical conductors for first andsecond layers 64, 66 include aluminum, carbon (such as graphite),cobalt, copper, gallium, gold, indium, iridium, iron, lead, magnesium,mercury (as an amalgam), nickel, niobium, palladium, platinum, rhenium,rhodium, selenium, silicon (such as highly doped polycrystallinesilicon), silver, tantalum, tin, titanium, tungsten, uranium, vanadium,zinc, zirconium, mixtures thereof, and alloys, oxides, or metalliccompounds of these elements. Preferably, first layer 64 is silver ink, anon-limiting example of which is ELECTRODAG® 427ss, commerciallyavailable from Acheson Colloids Company, Port Huron, Mich. Second layer66 is preferably a carbon ink, a non-limiting example of which is aconductive screen-printable ink of finely divided graphite particlesdispersed in a thermoplastic resin such as ELECTRODAG® 423ss orELECTRODAG® PM-003A, both commercially available from Acheson ColloidsCompany, Port Huron, Mich.

Cover substrate 21 is coupled to first surface 22 of sensor supportsubstrate 12. Cover substrate 21 includes a first surface 23 and asecond surface 25 facing sensor support substrate 12. In addition, coversubstrate 21 includes opposite ends 27, 29 and edges 31, 33 extendingbetween the ends 27, 29. Edge 31 includes a notch 35. Notch 35 is defiedby boundaries 37, 39, 41. When biosensor 10 is assembled, coversubstrate 21 cooperates with boundaries 78, 80, 82 of opening and sensorsupport substrate 12 to define a capillary channel.

Cover substrate 21 is generally rectangular in shape, it is appreciated,however, that the cover substrate may be formed in a variety of shapesand sizes in accordance with this disclosure. Cover substrate 21 isformed from a flexible polymer and preferably from a polymer such as apolyester or polyimide. A non-limiting example of a suitable polymer is3 mil thick clear MELINEX ST-505, coated with 3M fast-bond #30NF,thermoset adhesive. This adhesive is treated with 7% wt./wt. (TritonX-100 detergent).

Electrochemical reagent 20 is positioned on array 56. Reagent 20provides electrochemical probes for specific analytes. The choice ofspecific reagent 20 depends on the specific analyte or analytes to bemeasured, and are well known to those of ordinary skill in the art. Anexample of a reagent that may be used in biosensor 10 of the presentinvention is a reagent for measuring glucose from a whole blood sample.A non-limiting example of a reagent for measurement of glucose in ahuman blood sample contains 62.2 mg polyethylene oxide (mean molecularweight of 100-900 kilo Daltons), 3.3 mg NATROSOL 244M, 41.5 mg AVICELRC-591 F, 89.4 mg monobasic potassium phosphate, 157.9 mg dibasicpotassium phosphate, 437.3 mg potassium ferricyanide, 46.0 mg sodiumsuccinate, 148.0 mg trehalose, 2.6 mg TRITON X-100 surfactant, and 2,000to 9,000 units of enzyme activity per gram of reagent. The enzyme isprepared as an enzyme solution from 12.5 mg coenzyme PQQ and 1.21million units of the apoenzyme of quinoprotein glucose dehydrogenase.This reagent is further described in U.S. Pat. No. 5,997,817, thedisclosure of which is expressly incorporated herein by reference.

Non-limiting examples of enzymes and mediators that may be used inmeasuring particular analytes in biosensor 10 are listed below in Table1.

TABLE 1 Mediator Analyte Enzymes (Oxidized Form) Additional MediatorGlucose Glucose Dehydrogenase Ferricyanide and Diaphorase GlucoseGlucose-Dehydrogenase Ferricyanide (Quinoprotein) CholesterolCholesterol Esterase and Ferricyanide 2,6-Dimethyl-1,4- CholesterolOxidase Benzoquinone 2,5-Dichloro-1,4- Benzoquinone or PhenazineEthosulfate HDL Cholesterol Esterase Ferricyanide 2,6-Dimethyl-1,4-Cholesterol and Cholesterol Oxidase Benzoquinone 2,5-Dichloro-1,4-Benzoquinone or Phenazine Ethosulfate Triglycerides Lipoprotein Lipase,Ferricyanide or Phenazine Methosulfate Glycerol Kinase, and PhenazineGlycerol-3-Phosphate Ethosulfate Oxidase Lactate Lactate OxidaseFerricyanide 2,6-Dichloro-1,4- Benzoquinone Lactate LactateDehydrogenase Ferricyanide and Diaphorase Phenazine Ethosulfate, orFhenazine Methosulfate Lactate Diaphorase Ferricyanide PhenazineEthosulfate, or Dehydrogenase Phenazine Methosulfate Pyruvate PyruvateOxidase Ferricyanide Alcohol Alcohol Oxidase Phenylenediamine BilirubinBilirubin Oxidase 1-Methoxy- Phenazine Methosulfate Uric Acid UricaseFerricyanide

In some of the examples shown in Table 1, at least one additional enzymeis used as a reaction catalyst. Also, some of the examples shown inTable 1 may utilize an additional mediator, which facilitates electrontransfer to the oxidized form of the mediator. The additional mediatormay be provided to the reagent in lesser amount than the oxidized formof the mediator. While the above assays are described, it iscontemplated that current, charge, impedance, conductance, potential, orother electrochemically indicated property of the sample might beaccurately correlated to the concentration of the analyte in the samplewith biosensor 10 in accordance with this disclosure.

A plurality of biosensors 10 are typically packaged in a vial, usuallywith a stopper formed to seal the vial. It is appreciated, however, thatbiosensors 10 may be packaged individually, or biosensors can be foldedupon one another, rolled in a coil, stacked in a cassette magazine, orpacked in blister packaging.

Biosensor 10 is used in conjunction with the following:

1. a power source in electrical connection with tracks 60, 62 andcapable of supplying an electrical potential difference betweenelectrodes 52, 54 sufficient to cause diffusion limitedelectro-oxidation of the reduced form of the mediator at the surface ofthe working electrode; and

2. a meter in electrical connection with tracks 60, 62 and capable ofmeasuring the diffusion limited current produced by oxidation of thereduced form of the mediator with the above-stated electrical potentialdifference is applied.

The meter will normally be adapted to apply an algorithm to the currentmeasurement, whereby an analyte concentration is provided and visuallydisplayed. Improvements in such power source, meter, and biosensorsystem are the subject of commonly assigned U.S. Pat. No. 4,963,814,issued Oct. 16, 1990; U.S. Pat. No. 4,999,632, issued Mar. 12, 1991;U.S. Pat. No. 4,999,582, issued Mar. 12, 1991; U.S. Pat. No. 5,243,516,issued Sep. 7, 1993; U.S. Pat. No. 5,352,351, issued Oct. 4, 1994; U.S.Pat. No. 5,366,609, issued Nov. 22, 1994; White et al., U.S. Pat. No.5,405,511, issued Apr. 11, 1995; and White et al., U.S. Pat. No.5,438,271, issued Aug. 1, 1995, the disclosures of each of which areexpressly hereby incorporated by reference.

Many fluid samples may be analyzed. For example, human body fluids suchas whole blood, plasma, sera, lymph, bile, urine, semen, cerebrospinalfluid, spinal fluid, lacrimal fluid and stool specimens as well as otherbiological fluids readily apparent to one skilled in the art may bemeasured. Fluid preparations of tissues can also be assayed, along withfoods, fermentation products and environmental substances, whichpotentially contain environmental contaminants. Preferably, whole bloodis assayed with this invention.

A non-limiting method of manufacturing biosensor 10 is described below.A roll of thermoset-adhesive coated sensor support substrate material isfed into a punching unit where openings 34 and notches 36, 38 arepunched out. It is appreciated that a separate coating step can beperformed before the sensor support material substrate is fed into thepunching unit. It is appreciated that the sensor support substratepre-coated with a heat-sealable adhesive is also commercially available.

In a separate process, a roll of metallized electrode support materialis fed through guide rolls into an ablation/washing and drying station.A laser system capable of ablating electrode support substrate 14 isknown to those of ordinary skill in the art. Non-limiting examples ofwhich include excimer lasers, with the pattern of ablation controlled bymirrors, lenses, and masks. A non-limiting example of such a custom fitsystem is the LPX-300 or LPX-200 both commercially available from LPKFLaser Electronic GmbH, of Garbsen, Germany.

In the laser ablation station, the metallic layer of the metallized filmis ablated in a pre-determined pattern, to form a ribbon of isolatedelectrode sets on the electrode support material. To ablate electrodesin 50 nm thick gold conductor, 90 mJ/cm² energy is applied. It isappreciated, however, that the amount of energy required may vary frommaterial to material, metal to metal, or thickness to thickness. Theribbon is then passed through more guide rolls, with a tension loop andthrough an inspection system where both optical and electricalinspection can be made. The system is used for quality control in orderto check for defects. In that station, vent holes are also punchedthrough the electrode support substrate material.

The sensor support substrate material then fed into a cutting/laminationstation along with the electrode support substrate material. Theelectrode support substrate material cut into strips and then alignedwith the opening and notches of the sensor support substrate. Theelectrode support substrate is coupled to the sensor support substrateby a pressure and heat-sealing lamination process. Specifically, thealigned material is rolled against either a hot plate or a heat rollerto couple the sensor support substrate to the strips of the electrodesupport substrate material and form a sensor support/electrode supportsubassembly.

This sensor support/electrode support subassembly is then fed into ascreen or stencil printer equipped with IR drying stations. The silverink is applied as first electrically conductive tracks on the firstsurface 22 of the sensor support substrate 12. The silver ink is driedin a first IR dryer to cure the ink for approximately 2 minutes. Next,the carbon ink is applied as second electrically conductive tracts onthe first electrically conductive tracks. The carbon ink is also curedin the second IR drier for approximately 2 minutes.

Next, the sensor support/electrode support subassembly is fed into areagent dispensing station. The reagent 20 that has been compounded isfed into a dispensing station where it is applied in a liquid form tothe center of the array 56. Reagent application techniques are wellknown to one of ordinary skill in the art as described in U.S. Pat. No.5,762,770, the disclosure of which is expressly incorporated herein byreference. It is appreciated that the reagent may be applied to thearray 56 in a liquid or other form and dried or semi-dried onto thearray 56 in accordance with this disclosure.

A roll of cover substrate material is fed into a cutting/laminationstation along with the sensor support/electrode support subassembly. Thecover substrate material is cut into strips and then aligned with theopening of the sensor support substrate. The cover substrate is coupledto the sensor support substrate by a pressure and heat-sealinglamination process. Specifically, the aligned material is rolled againsteither a hot plate or a heat roller to couple the sensor supportsubstrate to the strips of the cover substrate material.

Next, the assembled material is fed into a sensor punch and packagingstation. In this station, the notches 35, 49 are formed in the coversubstrate 21 and the electrode support substrate 14 respectively as arethe tapers 83 leading to the opening 34 in the sensor support substrate12. The assembled material is punched to form individual biosensors 10,which arc sorted and packed into vials, each closed with a stopper, togive packaged biosensor strips.

In use, a user of biosensor 10 places a finger 109 having a bloodcollection incision against boundaries 39, 53 of notches 35, 49.Capillary forces pull a liquid blood sample 101 flowing from theincision into opening 34 and through the capillary channel acrossreagent 20 and array 56. The liquid blood sample 101 wets the reagent 20and engages electrode array 56, where the electrochemical reaction takesplace.

In use, after the reaction is complete, a power source (e.g., a battery)applies a potential difference between tracks 60, 62. The voltagetravels through layers 66, 64 and therefore between tracks 52, 54. Whenthe potential difference is applied, the amount of oxidized form of themediator at the auxiliary electrode and the potential difference must besufficient to cause diffusion-limited electro-oxidation of the reducedform of the mediator at the surface of the working electrode. A currentmeasuring meter (not shown) measures the diffusion-limited currentgenerated by the oxidation of the reduced form of the mediator at thesurface of the working electrode.

The measured current may be accurately correlated to the concentrationof the analyte in sample when the following requirements are satisfied:

1. The rate of oxidation of the reduced form of the mediator is governedby the rate of diffusion of the reduced form of the mediator to thesurface of the working electrode.

2. The current produced is limited by the oxidation of reduced form ofthe mediator at the surface of the working electrode.

FIGS. 3-4 illustrate an aspect of the invention in the form of abiosensor 110 having a sensor support substrate 112, an electrodesupport 114, the first electrical conductor 16 on the support 114,reagent (not shown) positioned on first conductor 16, a firstelectrically-conductive track 160 and a second electrically-conductivetrack 162 each extending across the support 112, and a cover 121.Biosensor 110 is preferably rectangular in shape. It is appreciated,however, that biosensor 110 can assume any number of shapes inaccordance with this disclosure. Biosensor 110 is preferably producedfrom rolls of material. Thus, the selection of materials for theconstruction of biosensor 110 necessitates the use of materials that aresufficiently flexible for roll processing, but which are still rigidenough to give a useful stiffness to finished biosensor 110.

Support 114 includes a top surface 140 facing sensor support substrate112 and a bottom surface 142. In addition, support 114 has opposite ends144, 146 and opposite edges 148, 150 extending between ends 144, 146.Edges 148, 150 and end 146 each include a notch 149 formed by agenerally concave-shaped boundary 151. While three concave shapednotches are illustrated, it is appreciated that support can includegreater or fewer than three notches and said notches can have a varietyof shapes and sizes in accordance with this disclosure. Support 114 isgenerally rectangular in shape, it is appreciated however, that supportmay be formed in a variety of shapes and sizes in accordance with thisdisclosure. Support 114 is formed from materials similar to electrodesupport substrate 14.

Electrodes 52, 54 cooperate with one another to define electrode array56 on surface 140 and leads 58, 59 that extend away from array 56 torespective contact pads 61, 63 at edges 148, 150. It is appreciated thatleads 58, 59 be formed to have a variety of lengths and extend to avariety of locations so that contact pads 61, 63 can be located onelectrode support substrate 114.

Sensor support substrate 112 of biosensor 110 includes a main portion116 and two sensor support substrate elements 118, 120. Main portion 116and sensor support substrate elements 118, 120 each include a firstsurface 122 and an opposite second surface 124 facing electrode support114 and edges 130, 132. In addition, main portion 116 of sensor supportsubstrate 112 has opposite ends 126, 128. Notches 136, 138 are formed inedges 130, 132 respectively and are each defined by boundaries 134, 135,137.

As shown in FIG. 4, when sensor support substrate 112 is coupled toelectrode support substrate 114, notches 136, 138 (as shown in FIG. 3)are in general alignment contact pads 61, 63 of electrodes 52, 54. It isappreciated that notches 136, 138 can be located in a number oflocations in sensor support substrate 112 and have a variety of shapesand sizes in accordance with this disclosure, so long as notches 136,138 are aligned, at least in part with contact pads 61, 63 whenbiosensor 110 is assembled. Sensor support substrate 112 is formed ofmaterials similar to sensor support substrate 12 and surface 124 of mainportion 116 and sensor support substrate elements 118, 120 are coatedwith adhesive similar to surface 24 of sensor support substrate 12. Itis also appreciated that sensor support substrate 112 may be printedwith, for example, product labeling or instructions for use inaccordance with this disclosure.

Referring again to FIG. 3, first and second tracks 160, 162 formed to bepositioned on first surface 122 of main portion 116. Tracks 160, 162each extend from end 126 and across respective notch 138, 136. Whiletrack 160, notch 138, and electrode 52 will be discussed hereafter, itis appreciated that unless indicated otherwise, the description appliesto track 162, notch 136, and electrode 54 as well. Track 160 includes afirst layer 164 and a second layer 166. Preferably first layer 164includes opposite ends 152, 154 and edges 156, 158 extending betweenends 152, 154. In addition, first layer 164 includes a generallytriangle-shaped contact area 168. When biosensor 110 is assembled, aportion of contact area 168 extends downwardly from first surface 122 ofsensor support substrate 112 into notch 138 and engages contact pad 63of electrode 52. In this manner, first layer 164 is in electricalcommunication with electrodes 52, 54 of support 114.

Second layer 166 of track 160 includes opposite ends 172, 174 and edges176, 178 extending between ends 172, 174. In addition, second layer 166includes a generally triangle-shaped contact area 180. A portion 182 ofcontact area 180 is aligned with the portion of contact area 168 thatengages electrode 52. Second layer 166, upon assembly of biosensor 110is in electrical communication with electrodes 52 via first layer 164.Materials suitable to construct first and second layers 164, 166 aresimilar to those used to construct layers 64, 66. In addition, whiledirect contact between track 160 and electrode 54 is illustrated anddescribed, it is appreciated track 160 and electrode 54 may not be indirect contact with one another so long as there is an electricalconnection between the two.

Cover 121 is coupled to first surface 122 of main portion 116 and sensorsupport substrate elements 118, 120. Cover 121 includes a first surface123 and a second surface 125 facing sensor support substrate 112. Inaddition, cover 121 includes opposite ends 127, 129 and edges 131, 133extending between the ends 127, 129. Edges 131, 133 and end 129 eachinclude a notch 184 formed by a generally concave-shaped boundary 186.When biosensor 110 is assembled, end 127 of cover is positioned overmain portion 116 of sensor support substrate 112. In addition, end 129of cover 121 is mounted on sensor support substrate elements 118, 120 ofsensor support substrate 112. Thus, three capillary channels are definedbetween cover 121 and electrode support 114 and intersect one another atarray 56. The first channel has an opening at ends 129, 146 and isdefined by cover 121, electrode support substrate 114, and sensorsupport substrate elements 118, 120. The second channel has an openingat edges 125, 148 and is defined by cover 121, electrode supportsubstrate 114, sensor support substrate element 120, and end 128 of mainportion 116. The third channel has an opening at edges 133, 150 and isdefined by cover 121, electrode support substrate 114, sensor supportsubstrate element 118, and end 128 of main portion 116.

Cover 121 is generally rectangular in shape, it is appreciated however,that cover 121 may be formed in a variety of shapes and sizes inaccordance with this disclosure. Cover 121 is formed from materialssimilar to cover substrate 21 and is coupled to electrode supportsubstrate 114 with an adhesive similar to the adhesive used to couplecover substrate 21 to electrode support substrate 14. In addition, it isappreciated that cover 121 may be formed with greater or fewer thanthree notches and said notches can have a variety of shapes and sizes inaccordance with this disclosure.

A non-limiting method of manufacturing biosensor 110 is described below.A roll of thermoset-adhesive coated sensor support substrate material isfed into a punching unit where notches 136, 138 and an opening ispunched out giving preliminary definition to main portion 116 and sensorsupport substrate elements 118, 120. A separate coating step can beperformed before the sensor support material substrate is fed into thepunching unit It is appreciated that the sensor support substratepre-coated with a heat-sealable adhesive also is commercially available.

The electrodes 52, 54 are formed on the electrode support substrate asdescribed above with reference to biosensor 10. The sensor supportsubstrate material then fed into a cutting/lamination station along withthe electrode support substrate material. The electrode supportsubstrate material is cut into strips and then aligned with the notchesof the sensor support substrate. The electrode support substrate iscoupled to the sensor support substrate by a pressure and heat-sealinglamination process. Specifically, the aligned material is rolled againsteither a hot plate or a heat roller to couple the sensor supportsubstrate to the strips of the electrode support substrate material andform a sensor support/electrode support subassembly.

The sensor support/electrode support subassembly is then fed into ascreen or stencil printer equipped with IR drying stations where tracks160, 162 are laid down upon surface 122 of the substrate material.Tracks 160, 162 are printed and cured similarly to tracks 60, 62. Next,the sensor support/electrode support subassembly is fed into a reagentdispensing station. The reagent is applied to the array as describedabove with reference to biosensor 10.

A roll of cover substrate material is fed into a cutting/laminationstation along with the sensor support/electrode support subassembly. Thecover substrate material is cut into strips and then aligned with themain portion 116 and the pre-defined sensor support substrate elements118, 120 to create capillary channels. The cover substrate is coupled tothe sensor support substrate by a pressure and heat-sealing laminationprocess. Specifically, the aligned material is rolled against either ahot plate or a heat roller to couple the sensor support substrate to thestrips of the cover substrate material.

Next, the assembled material is fed into a sensor punch and packagingstation. In this station, the notches 184, 149 are formed in therespective cover substrate 121 and the electrode support substrate 114.The assembled material is punched to form individual biosensors 110,which are sorted and packed into vials, each closed with a stopper, togive packaged biosensor strips.

Referring now to FIG. 4, a user of biosensor 110 places a finger 109having a blood collection incision against boundaries 151, 186 ofrespective notches 149, 184 at end 129. It is also appreciated, as shownby phantom arrows 188, 190, that the user can choose to place theirfinger against boundaries 151, 186 of respective notches 149, 184 atedges 148, 131; or 150, 133. Capillary forces pull the liquid bloodsample flowing from the incision through a capillary channel formedbetween cover 121, support 114, and sensor support substrate elements118, 120 toward array 56. The liquid blood wets the reagent (not shown)and engages array 56 where the electrochemical reaction takes place asdescribed above.

Biosensor 210 is shown in FIGS. 5-7. Biosensor 210 includes a sensorsupport substrate 212, an electrode support 214, firstelectrically-conductive material 16 positioned on support 214, reagent20 positioned on material 16, and first and second tracks 60, 62positioned on sensor support substrate 212 and in engagement withmaterial 16. Biosensor 210 is preferably a top-dose apparatus that isrectangular in shape. It is appreciated, however, that biosensor 210 canassume any number of shapes in accordance with this disclosure.

Support 214 is similar to electrode support substrate 14 except that ithas uninterrupted edges 248, 250 and ends 244, 246. Support 214 isconstructed of materials similar to electrode support substrate 14 asdescribed above. Support 214 is metallized with material 16 on topsurface 240. Referring to FIG. 5, material 16 on support 214 isdisrupted by laser ablation to form electrodes 252, 254. Electrodes 252,254 cooperate with one another to define an electrode array 256, leads258, 260 that extend away from array 256, and contact pads 261, 263.Leads 260, 258 extend away from array 256 to the contact pads 261, 263at respective edges 248, 250 of support 214. Reagent (not shown) extendsacross at least a portion of electrode array 256. In addition, it isappreciated that array 256 and contact pads 261, 263 can take on avariety of shapes and sizes and leads 258, 260 can be formed to have avariety of lengths and extend to a variety of locations to place contactpads 261, 263 in a variety of locations on support 214 in accordancewith this disclosure.

Sensor support substrate 212 of biosensor 210 is similar to substrates12, 112 except that it includes an opening 234 that extends betweenfirst and second surfaces 222, 224. See, FIGS. 5 and 7. A border 286defines opening 234. It is appreciated that the size, shape, andposition of opening 234 can vary in accordance with this disclosure.Sensor support substrate 212 is also formed to include notches 236, 238.When sensor support substrate 212 is coupled to support 214, opening 234is spaced-apart from array 256 and notches 236, 238 are aligned withelectrodes 254, 252 respectively. See FIGS. 6 and 7. It is appreciated,however, that opening 234 and notches 236, 238 can be located in anumber of locations in sensor support substrate 212 so long as notches236, 238 are aligned with contact pads 261, 263 in accordance with thisdisclosure. Preferably, sensor support substrate 212 is formed formmaterials similar to sensor support substrate 12 as described above andis coupled to support 214 with adhesive similar to the adhesive used tocouple sensor support substrate 12 to electrode support substrate 14.

Referring now to FIG. 7, sensor support substrate 212 is coupled to thesupport 214 in a particular pattern leaving an unsealed portion 223,which extends between boundary 236 and end 244. The adhesive-coatedsensor support substrate 212 and electrode support 214 inherently do notlie perfectly flat against one another, and therefore a capillarychannel 272 is created by default between unsealed portions 223 of thesensor support substrate 212 and the support 214. See FIG. 6. Thebiosensor 214 of the present invention takes advantage of surfaceirregularities of the sensor support substrate 212 and support 214 andthe thickness of the reagent to form capillary channel 272++++inc. byreference to move a liquid sample across the support 214 and toward theelectrode array 256.

A non-limiting method of manufacturing biosensor 210 is described below.A roll of thermoset-adhesive coated sensor support substrate material isfed into a punching unit where notches 236, 238 and opening 234 arepunched out. It is appreciated that a separate coating step can beperformed before the sensor support material substrate is fed into thepunching unit. It is appreciated that the sensor support substratepre-coated with a heat-sealable adhesive is also commercially available.

The electrodes 252, 254 are formed on the electrode support substrate asdescribed above with reference to biosensor 10. The sensor supportsubstrate material then fed into a cutting/lamination station along withthe electrode support substrate material. The electrode supportsubstrate material cut into strips and then aligned with the notches andopening of the sensor support substrate. The electrode support substrateis coupled to the sensor support by a pressure and heat-sealinglamination process. Specifically, the aligned material is rolled againsteither a hot plate or a heat roller to couple the sensor supportsubstrate to the strips of the electrode support substrate material andform a sensor support/electrode support subassembly.

The sensor support/electrode support subassembly is then fed a screen orstencil printer equipped with IR drying stations where tracks 60, 62 arelaid down upon surface 222 of the substrate material as described abovewith reference to biosensor 10. Next, the sensor support/electrodesupport subassembly is fed into a reagent dispensing station. Thereagent is applied to the array as described above with reference tobiosensor 10.

Next, the assembled material is fed into a sensor punch and packagingstation. In this station, the assembled material is punched to formindividual biosensors 210, which are sorted and packed into vials, eachclosed with a stopper, to give packaged biosensor strips.

In use, a user of biosensor 210 places a finger into opening 234 anddeposits a liquid blood sample. Capillary forces pull the liquid samplethrough the channel 272 created by unsealed portion 223 toward array256. The liquid blood sample wets the reagent (not shown) and engagesthe electrode array 256, where the electrochemical reaction takes placeas previously described.

Biosensor 310 is shown in FIGS. 8-9. Biosensor 310 includes sensorsupport substrate 212, electrode support 214, firstelectrically-conductive material 16 positioned on support 214, thereagent (not shown) positioned on material 16, and first and secondtracks 60, 62 positioned on sensor support substrate 212 and inengagement with material 16. Biosensor 310 is preferably a top-doseapparatus that is rectangular in shape. It is appreciated, however, thatbiosensor 310 can assume any number of shapes in accordance with thisdisclosure.

Biosensor 310 is similar to biosensor 210 except that the electricallyconductive material 16 on support 214 is disrupted by laser ablation toform electrodes 352, 354. Electrodes 352, 354 cooperate with one anotherto define spaced-apart electrode arrays 356, 258, leads 360, 362 thatextend away from arrays 356, 358, and contact pads 361, 363. Leads 360,362 extend away from arrays 356, 358 to contact pads 361, 363 atrespective edges 248, 250 of support 214. The reagent (not shown) ispositioned to extend across electrode array 356. In addition, it isappreciated that arrays 356, 358 can take on a variety of shapes andsizes and leads 360, 362 be formed to have a variety of lengths andextend to a variety of locations on support 214 in accordance with thisdisclosure.

Biosensor 310 is manufactured similarly to biosensor 210, except for thestep of ablating the electrically conductive material 16 from theelectrode support 214. To form electrodes 352, 354, the metallic layerof the metallized film is ablated in a pre-determined electrode pattern,to form arrays 356, 358, leads 360, 362 that extend from arrays 356,358, and contact pads 361, 363. As with biosensor 10, 110, 210, theassembled material is fed into a sensor punch and packaging station. Inthis station, the assembled material is punched to form individualbiosensors 310, which are sorted and packed into vials, each closed witha stopper, to give packaged biosensor strips.

In use, a user of biosensor 310 places a finger into opening 234 anddeposits a liquid blood sample onto array 358. Capillary forces pull theliquid sample through the channel 272, across array 358 whereinterference corrections may be made and toward array 356. The liquidblood sample wets the reagent (not shown) and engages electrode array356, where an electrochemical reaction takes place as previouslydescribed.

The processes and products described above include disposable biosensors10, 110, 210, 310, especially for use in diagnostic devices. Alsoincluded, however, are electrochemical sensors for non-diagnostic uses,such as measuring an analyte in any biological, environmental, or othersample. As discussed above, biosensors 10, 110, 210, 310 can bemanufactured in a variety of shapes and sizes and be used to perform avariety of assays, non-limiting examples of which include current,charge, impedance conductance, potential or other electrochemicalindicative property of the sample applied to biosensor.

Although the invention has been described in detail with reference to apreferred embodiment, variations and modifications exist within thescope and spirit of the invention, on as described and defined in thefollowing claims.

What is claimed is:
 1. An electrochemical biosensor comprising: anelectrode support substrate, electrodes positioned on the electrodesupport substrate, a sensor support substrate coupled to the electrodesupport substrate, the sensor support substrate having a first surface,and opposite second surface facing the electrode support substrate, andnotches extending between the first and second surfaces, each notchbeing aligned with a portion of one electrode, a capillary channel, atleast a portion of the electrodes being positioned in the capillarychannel, and electrically conductive tracks positioned on the firstsurface of the sensor support substrate, a portion of each trackextending from the first surface into at least one notch and being inelectrical communication with one of the electrodes.
 2. The biosensor ofclaim 1 wherein the electrodes cooperate to define an electrode arrayand leads extending from the array and each notch is aligned with atleast a portion of one lead.
 3. The biosensor of claim 1 wherein theelectrodes cooperate to define spaced-apart electrode arrays.
 4. Thebiosensor of claim 3 wherein the sensor support substrate is formed toinclude an opening in alignment with one of the electrode arrays.
 5. Thebiosensor of claim 1 wherein the tracks are formed to include layers. 6.The biosensor of claim 5 wherein one layer is silver ink.
 7. Thebiosensor of claim 5 wherein one layer is carbon ink.
 8. The biosensorof claim 5 wherein the electrodes are gold.
 9. The biosensor of claim 1wherein the sensor support substrate is formed to include an opening inalignment with at least a portion of the electrodes.
 10. The biosensorof claim 9 further comprising a cover substrate coupled to the sensorsupport substrate.
 11. The biosensor of claim 10 wherein the coversubstrate, sensor support substrate, and electrode support substratecooperate with one another to define channel.
 12. The biosensor of claim1 wherein the electrode support substrate and the sensor supportsubstrate cooperate to define the channel.
 13. A biosensor comprising: ametallized electrode support substrate being formed to define anelectrode array and leads extending from the array, a sensor supportsubstrate coupled to the electrode support substrate, the sensor supportsubstrate being formed to include notches and an opening, at least aportion of each notch being aligned with one lead and the opening beingspaced-apart from the leads, and electrically conductive trackspositioned on the sensor support substrate, each track extending acrossone of the notches and into engagement with one lead.
 14. The biosensorof claim 13 wherein the tracks are formed to include layers.
 15. Thebiosensor of claim 14 wherein one layer is silver ink.
 16. The biosensorof claim 14 wherein one layer is carbon ink.
 17. The biosensor of claim14 wherein the electrode array and leads are gold.
 18. The biosensor ofclaim 14 further comprising a cover substrate coupled to the sensorsupport substrate and extending across the electrode array.
 19. Abiosensor comprising: an electrode support substrate being formed todefine an electrode array and leads extending from the array, a sensorsupport substrate positioned on the electrode support substrate, thesensor support substrate being formed to include notches and an opening,at least a portion of each notch being aligned with one lead and theopening being spaced-apart from the leads, and electrically conductivetracks positioned on the sensor support substrate, each track extendingacross one of the notches and into engagement with one lead.
 20. Thebiosensor of claim 19 wherein the tracks are formed to include layers.21. The biosensor of claim 20 wherein one layer is silver ink.
 22. Thebiosensor of claim 20 wherein one layer is carbon ink.
 23. The biosensorof claim 20 wherein the electrode array and leads are gold.
 24. Thebiosensor of claim 20 further comprising a cover substrate coupled tothe sensor support substrate and extending across the electrode array.